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An increasing number of patients are being diagnosed with multiple ground glass opacities (GGOs), but a consensus on the treatment of these patients is still lacking. The aim of this study was to investigate the safety and feasibility of a novel technique, electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation combined with uniportal video-assisted thoracoscopic surgery in patients with multiple GGOs. The clinical, radiographic, surgical, and pathologic data of patients with multiple GGOs who underwent ENB-guided microwave ablation combined with uniportal video-assisted thoracoscopic surgery from October 2018 to December 2019 were reviewed. Eleven patients with multiple GGOs underwent ENB-guided microwave ablation combined with uniportal video-assisted thoracoscopic surgery; they included 6 men and 5 women with a mean age of 61.3 ± 5.1 years (range, 53 to 68). Thirty-seven lesions were observed in the 11 patients, 21 of which were microwave ablated and 16 of which were surgically resected. Only 1 patient had postoperative pneumothorax and subcutaneous emphysema and was successfully discharged from the hospital after symptomatic treatment. The success rate and the efficiency of microwave ablation under ENB guidance were both 100%, with no other serious complications or procedure-related deaths occurring. No local metastasis or recurrence occurred in any patients during the follow-up period. Electromagnetic navigation bronchoscopy-guided microwave ablation combined with uniportal video-assisted thoracoscopic surgery is safe and feasible in patients with multiple GGOs suspected of having multiple primary lung cancers, and may represent an alternative approach for more patients, particularly patients who cannot tolerate the simultaneous resection of multiple tumors. [Display omitted] [ABSTRACT FROM AUTHOR]